Dystrophin

Dystrophin is a rod-shaped cytoskeletal protein that connects the intercellular cytoskeleton to the extracellular matrix through an actin-associated glycoprotein complex. This property enables Dystrophin to play a role in sarcolemmal stability during muscle contraction and prevent contraction damage. Dystrophin also mediates cell signaling, such as mechanotransduction and cell adhesion. However, Dystrophin deficiency or mutation (producing internally truncated Dystrophin) will become a predisposing factor for Duchenne muscular dystrophy (DMD). In the muscle tissue of mild and asymptomatic patients, a large number of alternative Dystrophin splicing protein products can be detected. Currently, the methods for restoring Dystrophin mutations rely on virus-mediated restoration or exon skipping. Exon skipping uses antisense oligonucleotides to induce alternative splicing, bypassing the mutated exon to restore the protein reading frame, and converting DMD mutations to Becker muscular dystrophy (BMD) protein mutations.
Dystrophin-related proteins can be divided into three groups (according to subcellular localization): (1) α-dystroglycan located outside the cell; (2) β-dystroglycan, sarcoglycans, and sarcospan located on the plasma membrane; (3) Dystrophin, dystrobrevin, syntrophins, and neuronal nitric oxide synthase located inside the cell. Dystrophin has four major functional domains: the actin-binding amino-terminal domain (ABD1), the central rod domain, the cysteine-rich domain, and the carboxyl terminus. Dystrophin interacts with tubulin and acidic actin filaments through the rod domain, so Dystrophin mutations not only lead to progressive loss of muscle tissue and function, but also cause cardiomyopathy^[1][2][3].

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